Congenital heart defects are the most common birth defects in newborns. Understanding of the molecular basis of heart development has increased dramatically in the last decade. Proper patterning of the heart and its associated vasculature results from a complex series of signaling events and tissue interactions. Recent evidence generated by our lab and others demonstrates an important role for Fgf8 in cardiovascular patterning. Gbx2, which encodes a homeobox-containing transcription factor, is expressed in overlapping domains with Fgf8 and is inducible by FGF8. Preliminary data generated in our lab also suggests that Gbx2, like Fgf8, is necessary for cardiovascular development. Furthermore, Gbx2-/-;Fgf8 embryos exhibit an increased frequency of cardiovascular defects, suggesting a genetic interaction between Gbx2 and Fgf8 during development. We propose to examine the role of Gbx2 in cardiovascular development as well as the potential interaction with Fgf8 during this event. Using a variety of morphological and molecular analyses, we will examine Gbx2-/- and Gbx2-/-;Fgf8 embryos to determine the pathogenesis of cardiovascular defects in these mutants.